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1.
Rev. patol. respir ; 23(supl.1): S1-S4, feb. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-188028

RESUMO

Las guías de práctica clínica (GPC) aparecieron con el fin de homogenizar el diagnóstico y tratamiento del asma; inicialmente como un consenso de expertos, y posteriormente incluyendo para sus afirmaciones y recomendaciones técnicas de medicina basada en la evidencia, e incorporar en sus actualizaciones frecuentes, los cambios en el conocimiento fisiopatológico y en el manejo de la enfermedad. En el 2019 se han realizado actualizaciones de las tres principales GPC incluyendo el tratamiento del paciente con asma grave no controlada, el uso de fármacos biológicos y otros procedimientos


The clinical practice guidelines (CPG) appeared with the intention to homogenize the asthma diagnosis and treatment, initially as an expert consensus, and afterwards including evidence based medicine data for its affirmations and technical recommendations incorporating advances in knowledge and management of the disease in their frequent updates. In 2019 the 3 principal CPG, have updates including the management of non-controlled severe asthma patients, biological treatments use and other procedures


Assuntos
Humanos , Asma/terapia , Guias de Prática Clínica como Assunto , Consenso , Recidiva , Produtos Biológicos/uso terapêutico , Glucocorticoides/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Imunoglobulina E/uso terapêutico , Interleucina-5/uso terapêutico , Interleucina-4/uso terapêutico , Azitromicina/uso terapêutico , Termoplastia Brônquica/métodos
2.
Allergol. immunopatol ; 47(3): 209-213, mayo-jun. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-186479

RESUMO

Introduction: There is accumulated evidence supporting a beneficial role of Mediterranean diet (MD) in the control of asthma symptoms. The aim of this study was to investigate the relationships between adherence to MD and serum levels of certain cytokines namely, interleukin (IL)-4, and IL-17 known to have a pathogenetic role in the airway changes associated with asthma. Methods: We measured serum IL-4, IL-33, and IL-17, in 44 asthmatic and 26 healthy children, 5-15 years old. Their adherence to MD was estimated with the Mediterranean Diet Quality Index for children and adolescents (KIDMED) score. Results: KIDMED score did not differ between the two groups (P = 0.59) and was not correlated with any of the three measured cytokines. However, when the analysis was restricted only to asthmatic children, the KIDMED score was correlated with IL-4, IL-33, and IL-17 (Beta: -0.56, P = 0.007; Beta: 0.57, P = 0.010; Beta: -0.62, P = 0.017, respectively). Conclusion: Our results indicate that MD can modulate the production of some of the main inflammatory mediators of asthma, in asthmatic children


No disponible


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Asma/dietoterapia , Dieta Mediterrânea , Cooperação do Paciente/estatística & dados numéricos , Asma/epidemiologia , Grécia/epidemiologia , Mediadores da Inflamação/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Fatores de Risco , Inquéritos e Questionários
3.
Allergol. immunopatol ; 47(3): 234-240, mayo-jun. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-186483

RESUMO

Introduction and objectives: Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes. Patients and methods: This case-control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA). Results: OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32 ± 19.21% vs. 2.79 ± 2.48% respectively, p < 0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p < 0.01 - p < 0.05) respectively. Conclusions: Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis


No disponible


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Linfócitos B/imunologia , Biomarcadores/sangue , Imunoglobulina E/sangue , Interleucina-4/sangue , Ligante OX40/metabolismo , Rinite Alérgica/imunologia , Células Th2/imunologia , Antígenos CD4/metabolismo , Estudos de Casos e Controles , Regulação para Cima , Células Cultivadas
4.
Allergol. immunopatol ; 47(2): 172-178, mar.-abr. 2019. graf, tab
Artigo em Inglês | IBECS | ID: ibc-180806

RESUMO

Background: Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency (PID). LPS-responsive beige-like anchor protein (LRBA) deficiency is an autosomal recessive disease characterized by a CVID-like phenotype. T cell abnormality was reported in patients with CVID and LRBA deficiency. The study's aim was to evaluate IL-4, IL-5, IL-10 and GATA3 expression in patients with LRBA deficiency and CVID with no known monogenic disease, and further evaluate its relevance with immunological futures and clinical complications of patients. Methods: The study population comprised patients with CVID, LRBA deficiency and age-sex matched healthy controls. Mutation analysis was done by whole exome sequencing in CVID patients to rule out monogenic PIDs. After CD4+ T cell stimulation with anti-CD3 and anti-CD28 monoclonal antibodies, gene expression of IL-4, IL-5, IL-10 and transcription factor GATA3 was evaluated by real-time polymerase chain reaction. The protein of mentioned cytokines was assessed by enzyme-linked immunosorbent assay. Results: The main clinical presentations of CVID patients were infections only and lymphoproliferations phenotypes, but in LRBA patients were autoimmune and enteropathy phenotype. The frequencies of CD4+ T cells were significantly reduced in LRBA and CVID patients. There were no statistically significant differences among GATA3, IL4, and IL5 gene expressions by CD4+ T cells of patients and controls, however, the IL10 expressions in CVID patients was significantly lower than in LRBA patients and HCs. As compared with HCs, CVID patients showed a prominent decrease in IL-4 and IL-10 production by CD4+ T cells. Conclusions: Our findings demonstrated that patients with CVID and LRBA deficiency (even with severe infectious and inflammatory complications) have not imbalance in Th2 response, which is in parallel with lower frequency of allergy and asthma in these patients


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Proteínas Adaptadoras de Transdução de Sinal/genética , Linfócitos T CD4-Positivos/fisiologia , Imunodeficiência de Variável Comum/genética , Fator de Transcrição GATA3/genética , Interleucina-10/genética , Interleucina-4/genética , Interleucina-5/genética , Autoimunidade , Análise Mutacional de DNA , Células Cultivadas , Análise Mutacional de DNA , Progressão da Doença
5.
Actas dermo-sifiliogr. (Ed. impr.) ; 109(3): 230-240, abr. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-172828

RESUMO

La dermatitis atópica (DA) es una frecuente enfermedad crónica e inflamatoria de la piel que acarrea una fuerte carga física y emocional. La DA suele comenzar a edades tempranas y tiene un curso heterogéneo. Las últimas evidencias a este respecto sugieren que las interleucinas IL-4 e IL-3 son citoquinas claves en la inmunopatogénesis de la DA. El dupilumab es un anticuerpo monoclonal dirigido contra la subunidad del receptor alfa de la IL-4 que bloquea la señalización tanto de la IL-4 como de la IL-3. Datos extraídos de estudios fase i-iii revelan que administrado como monotratamiento o acompañado de corticosteroides tópicos, el dupilumab se tolera bien y resulta efectivo en el tratamiento de pacientes adultos con DA de carácter entre moderado y grave. Un gran número de pacientes que recibieron dupilumab experimentaron mejorías notables en varios índices de eficacia, incluidos el Índice de gravedad y área de eccema, la Escala de evaluación global del investigador y la Escala de dermatitis atópica. Estos resultados abren una nueva era a tratamientos dirigidos en el manejo de la DA


Atopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. AD usually starts in early childhood and has a heterogeneous course. Emerging evidence suggests that IL-4 and IL-13 are key cytokines in the immunopathogenesis of AD. Dupilumab is a monoclonal antibody directed against IL-4 receptor α subunit, that blocks both IL-4 and IL-13 signaling. Data from Phase I-III studies revealed that dupilumab, administered as monotherapy or with topical corticosteroids, is effective and well tolerated in the treatment of adult patients with moderate-to-severe AD. A large proportion of patients receiving dupilumab had significant improvements in multiple efficacy indexes, including Eczema Area and Severity Index, Investigator's Global Assessment and SCORing Atopic Dermatitis scores. These results introduce a new era of targeted therapies in the management of AD


Assuntos
Humanos , Dermatite Atópica/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Terapia Biológica/métodos , Corticosteroides/uso terapêutico , Interleucina-4/uso terapêutico , Interleucina-13/uso terapêutico
6.
J. investig. allergol. clin. immunol ; 28(3): 139-150, 2018. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-174448

RESUMO

Moderate and severe forms of allergic diseases such as atopic dermatitis and asthma are a challenge for clinicians. In these conditions, which severely affect the quality of life of the patient and frequently have associated allergic comorbidities, the therapeutic options are often very limited. Treatment with systemic corticosteroids and immunosuppressants has adverse effects in the long term, and a significant proportion of patients remain refractory to therapy. In this context, the emerging biological drugs constitute a truly innovative therapeutic approach. A leading example is dupilumab, a monoclonal antibody targeting the α chain of the interleukin (IL)-4 receptor. Dupilumab inhibits the biological effects of the cytokines IL-4 and IL-13, which are key drivers in the TH2 response. The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. In 2017, the United States Food and Drug Administration and the European Medicines Agency approved the use of dupilumab for the treatment of adult patients with moderateto-severe atopic dermatitis whose disease is not adequately controlled with prescribed topical treatment. The results of phase III clinical studies of dupilumab in patients with persistent, uncontrolled asthma have been highly promising. The safety and tolerability profile of dupilumab has proven to be very favorable in long-term clinical trials. In this review, we focus on the mechanism of action of dupilumab, its development, and its impact on daily clinical practice in allergic diseases


Las formas clínicas moderadas y graves de enfermedades alérgicas comunes como la dermatitis atópica o el asma constituyen un reto para los clínicos. En estos casos, que afectan intensamente la calidad de vida del paciente y con frecuencia conllevan otras enfermedades alérgicas asociadas, las opciones terapéuticas son a menudo muy limitadas. El tratamiento con corticosteroides sistémicos o inmunosupresores tiene efectos adversos a largo plazo y una proporción significativa de pacientes se muestra refractaria a la terapia. En este contexto, los nuevos fármacos biológicos, dirigidos a la base inmunológica de la enfermedad, ofrecen un enfoque terapéutico verdaderamente innovador. Un ejemplo destacado de estos fármacos es dupilumab, un anticuerpo monoclonal dirigido contra la cadena alfa del receptor de la interleucina (IL)-4. Dupilumab inhibe los efectos biológicos de las citoquinas IL-4 e IL-13, unos de los principales efectores de la respuesta Th2. La efectividad y seguridad de dupilumab en el tratamiento de enfermedades alérgicas se han probado durante más de diez años en una variedad de grandes ensayos clínicos en dermatitis atópica, asma, rinosinusitis crónica con poliposis nasal y esofagitis eosinofílica. La FDA y la EMA aprobaron en 2017 el uso de dupilumab en el tratamiento de pacientes adultos con dermatitis atópica moderada o grave que no se controla adecuadamente con tratamiento tópico. Los estudios clínicos de Fase 3 de dupilumab en pacientes con asma persistente no controlada también han sido muy prometedores. En los ensayos clínicos a largo plazo la seguridad y tolerabilidad de dupilumab ha demostrado ser muy elevada. En esta revisión nos hemos centrado en el mecanismo de acción de dupilumab, su desarrollo como fármaco y su impacto en la terapia de enfermedades alérgicas


Assuntos
Humanos , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Terapia Biológica/métodos , Produtos Biológicos/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Asma/tratamento farmacológico , Interleucina-4/antagonistas & inibidores , Interleucina-13/antagonistas & inibidores , Células Th2/imunologia
7.
J. investig. allergol. clin. immunol ; 28(6): 407-413, 2018. tab
Artigo em Inglês | IBECS | ID: ibc-174554

RESUMO

Background: Asthma is a complex and heterogeneous disease. We found gene-gene interactions between IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 in asthmatic Chinese Han children. This 4-locus set constituted an optimal statistical interaction model. Objective: We examined associations between the 4-gene model (IL13, IL4, FCER1B, and ADRB2) and the Asthma Predictive Index (API) and atopy in Chinese Han children. Methods: Four single-nucleotide polymorphisms in the 4 genes were genotyped in 385 preschool children with wheezing symptoms using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The t test and x2 tests were used for the analysis. Results: Significant correlations were found between the 4-locus gene model and a stringent and loose API (both P<.0001). Additionally, a high-risk asthma genotype was a risk factor for a positive API (stringent API, OR=4.08; loose API, OR=2.36). We also found a statistically significant association between the 4-locus gene model and atopy (P<.01, OR=2.09). Conclusions: Our results indicated that the 4-locus gene model consisting of L13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was associated with the API and atopy. These findings provide evidence that this gene model can be used to determine a high risk of developing asthma and atopy in Chinese Han children


Antecedentes: El asma es una enfermedad compleja y heterogénea. En este estudio, encontramos que las interacciones gen-gen entre IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713 y FCER1B rs569108, en niños asmáticos de nacionalidad china Han, constituyen un modelo estadístico óptimo de interacción. Objetivo: Este estudio examinó un modelo de las asociaciones de cuatro genes (IL13, IL4, FCER1B y ADRB2) con el Índice Predictivo de Asma (IPA) y la atopia en niños Han chinos. Métodos: Se genotiparon cuatro polimorfismos de un solo nucleótido (SNP) en los cuatro genes, en 385 niños en edad preescolar con síntomas de sibilancias, utilizando espectrometría de masas con desorción/ionización mediante láser asistida por Matriz (MALDI). Para el análisis estadístico de utilizaron el test t de Student y el c2. Resultados: Se encontraron correlaciones significativas entre el modelo génico de los cuatro locus y el valor de IPA estricto y laxo (ambos P <0,0001). Además, el genotipo de riesgo alto de asma fue un factor de riesgo para IPA positivo (IPA estricto: OR = 4,08, IPA laxo: OR = 2,36). También, encontramos una asociación estadísticamente significativa entre el modelo génico de los cuatro locus, con atopia (P <0,01, OR = 2,09). Conclusiones: Nuestros resultados indicaron que el modelo génico de cuatro locus compuesto por L13 rs20541, IL4 rs2243250, ADRB2 rs1042713 y FCER1B rs569108 estaba asociado con IPA y atopia. Estos hallazgos proporcionan la evidencia de la utilidad de este modelo génico para determinar el riesgo alto de desarrollar asma y atopia en niños chinos Han


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Asma/epidemiologia , Hipersensibilidade Imediata/epidemiologia , Loci Gênicos/genética , Interleucina-4/genética , Interleucina-13/genética , Receptores Adrenérgicos beta/genética , Fragmentos Fc das Imunoglobulinas/genética , China/epidemiologia , Marcadores Genéticos , Predisposição Genética para Doença/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único/genética
8.
Allergol. immunopatol ; 45(supl.1): 45-49, dic. 2017.
Artigo em Inglês | IBECS | ID: ibc-170235

RESUMO

Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids and with a second controller drug to prevent it from becoming uncontrolled or which remains uncontrolled despite this therapy. Patients with uncontrolled severe asthma require additional treatment options as add-on therapy, including biologics. Biologic therapies in asthma are designed to block key immune regulators, such as IgE, or certain pro-inflammatory cytokines, e.g. interleukin (IL)-5, IL-4, IL-13 or IL-17. Patients with severe asthma and eosinophilic phenotype may benefit from biologic therapies aimed at reducing blood and tissue eosinophils, such as mepolizumab, reslizumab and benralizumab. Patients with Th2-high phenotype may also benefit from therapy with anti-IL-4/anti-IL-13 monoclonal antibodies (dupilumab). The main limitations of asthma treatment with biologic agents are the crossover and overlap of the different pathways in the pathogenesis of asthma which may cause lack of complete success of these therapies, in addition of high costs, which make pharmacoeconomic studies necessary to identify the ideal target patient population to receive these biologic drugs (AU)


No disponible


Assuntos
Humanos , Terapia Biológica/métodos , Asma/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Interleucina-5/imunologia , Imunoglobulina E/imunologia , Interleucina-4/imunologia , Interleucina-13/imunologia
9.
Allergol. immunopatol ; 45(4): 350-355, jul.-ago. 2017. graf, ilus
Artigo em Inglês | IBECS | ID: ibc-165094

RESUMO

Background: Medical gas hydrogen (H2) has a special role in airway inflammation; however, the effect of H2on allergic rhinitis (AR) remains unclear. This study explored the possible roles of H2 on the pathogenesis of AR and observed the influences of H2 on cytokines IL-4 and IL-13. Methods: An AR guinea pig model was established by nasal ovalbumin sensitisation. Eighteen guinea pigs were divided into three groups, namely, saline control, AR-sensitised, and hydrogen-rich saline (HRS)-treated groups, with each group having six guinea pigs. The frequencies of sneezing and scratching were recorded. The IgE level and cytokine (IL-4 and IL-13) levels in the serum were measured. The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also determined by real-time reverse transcriptase-polymerase chain reaction and Western blot. We also observed the infiltration of cytokine (IL-4 and IL-13) in nasal mucosa by immunofluorescence. Results: The frequencies of sneezing and scratching, as well as the levels of IgE, IL-4, and IL-13, in the serum were higher in the AR group than in the control group (p < 0.01), whereas all these parameters were decreased significantly after HRS treatment (p < 0.05). The expression levels of IL-4 and IL-13 mRNA and protein in the nasal mucosa were also lower in guinea pigs treated with HRS than those in the AR group (p < 0.05). Conclusions: HRS could affect anti-inflammation in AR and decreased the expression of IL-4 and IL-13 (AU)


No disponible


Assuntos
Animais , Rinite Alérgica/imunologia , Interleucina-4/análise , Interleucina-13/análise , Hidrogênio/farmacocinética , Modelos Animais de Doenças , Biomarcadores/análise , Estudos de Casos e Controles , Imunofluorescência , Imunoglobulina E/análise
10.
Med. oral patol. oral cir. bucal (Internet) ; 22(1): e1-e6, ene. 2017. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-159760

RESUMO

Background: It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. Material and Methods: Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. Results: In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. Conclusions: In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells (AU)


No disponible


Assuntos
Humanos , Carcinoma de Células Gigantes/patologia , Interleucina-4/farmacocinética , Neoplasias Mandibulares/patologia , Granuloma de Células Gigantes/patologia , Monócitos/patologia , Cadeias beta de Integrinas/análise , Células Gigantes/patologia , Leucócitos Mononucleares/patologia , Estudos de Casos e Controles
11.
Allergol. immunopatol ; 44(1): 23-31, ene.-feb. 2016. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-147480

RESUMO

Background: House dust mites (HDMs) faeces are the main factor involved in respiratory disorder. The true HDMs,Dermatophagoides pteronyssinus and D. farinae, detected in the samples collected from the house dust are the most important causes of allergic disorders such as asthma. Objective: The aim of this investigation was to study the curcuma and karkade amelioration of the allergenic immunological disorder, especially some cytokines, IgE and ROS, caused by the faeces of the dominant true HDM, D. pteronyssinus and D. farinae in valley and desert houses in EL-Minia Governorate, respectively. Methods: HDM cultures, faeces isolation, plant extraction and ELISA techniques were used. Male albino rats were classified into control, inhaled, and treated groups. Results: The present immunological study on the dominant allergenic true HDMs, D. pteronyssinus and D. farinae, revealed that significantly higher serum levels of TNF-α, IL-1β, IL-4, IL-13 and IgE were found in rats treated with both D. pteronyssinus and D. farinae faeces than the other groups. In addition, statistical analysis of ROS data showed significant difference between the curcuma- and karkade-treated groups and either the control or the faeces-treated groups (P < 0.05). Conclusions: Some immunological disturbances caused by repeated exposure to the faeces of two dominant allergenic true HDM species (D. pteronyssinus and D. farinae) in the valley and desert houses could be ameliorated by curcuma and karkade (AU)


No disponible


Assuntos
Animais , Masculino , Feminino , Ratos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/imunologia , Asma/diagnóstico , Infestações por Ácaros/epidemiologia , Infestações por Ácaros/imunologia , Infestações por Ácaros/prevenção & controle , Ácaros/imunologia , Asma/imunologia , Asma/veterinária , Linfotoxina-alfa/imunologia , Linfotoxina-alfa/isolamento & purificação , Interleucina-4 , Interleucina-13/imunologia , Interleucina-13/isolamento & purificação , Interleucina-1/imunologia , Imunoglobulina E/análise , Imunoglobulina E/imunologia
12.
Arch. bronconeumol. (Ed. impr.) ; 51(11): 571-578, nov. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-144372

RESUMO

Introducción: El asma es una afección inflamatoria de las vías respiratorias. Las infecciones porMycoplasma pneumoniae pueden exacerbar los síntomas del asma. Se ha demostrado que la interleucina2 y la interleucina4 participan en las reacciones inmunitarias e inflamatorias. Hemos estudiado la relación entre los polimorfismos de la IL2 y la IL4 y su expresión y el riesgo de padecer asma e infección por M.pneumoniae en niños. Métodos: Se reclutó a 392 niños asmáticos y 849 controles para el estudio. Se genotiparon 8 polimorfismos en IL2 e IL4 con la plataforma MassARRAY de Sequenom. La infección por M.pneumoniae y el número de copias se establecieron mediante PCR fluorescente. Los niveles séricos de expresión de IL-2 e IL-4 se midieron con ELISA. Resultados: Hallamos una relación significativa entre el polimorfismo rs6534349 de IL2 y el aumento de riesgo de sufrir asma (heterocigóticos, p = 0,029; variantes homocigóticas, p = 0,013), así como entre el polimorfismo rs2227284 de IL4 y una reducción del riesgo de padecer asma (heterocigóticos, p = 0,026; variantes homocigóticas, p = 0,001). Además, la relación con otros polimorfismos, excepto el rs2070874, se hizo evidente al agrupar a los niños asmáticos según la clasificación GINA de control y gravedad del asma. Asimismo, los niveles séricos de expresión de IL-2 e IL-4 fueron significativamente mayores en los sujetos no infectados (p = 0,038) e infectados (p = 0,011) por M.pneumoniae, respectivamente. Esta observación también se cumple entre los pacientes asmáticos (p = 0,016 para IL-2 y p = 0,042 para IL-4), pero en los controles no asmáticos solo se cumple en el caso de la IL-4 (p = 0,032). Del mismo modo, observamos que el genotipo GG rs6534349 estaba claramente relacionado con un aumento de las posibilidades de tener una infección con alta carga de M.pneumoniae (p = 0,0376). Conclusiones: La IL2 y la IL4 podrían ser biomarcadores importantes para calcular el riesgo de padecer asma, así como infección por M.pneumoniae, en niños


Introduction: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 andIL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children. Methods: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms inIL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA. Results: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P = .029; homozygous variants; P = .013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P = .026; homozygous variants; P = .001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P = .038) and positive (P = .011) subjects respectively. This observation holds true among asthmatic patients (P = .016 for IL-2 and P = .042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P = .032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P = .0376). Conclusions: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children


Assuntos
Criança , Humanos , Asma/imunologia , Infecções por Mycoplasma/epidemiologia , Mycoplasma pneumoniae/patogenicidade , Interleucina-4/análise , Interleucina-2/análise , Polimorfismo Genético , Fatores de Risco , Suscetibilidade a Doenças/imunologia
13.
Allergol. immunopatol ; 43(5): 482-486, sept.-oct. 2015. tab, graf
Artigo em Inglês | IBECS | ID: ibc-141110

RESUMO

Introduction: Asthma is an inflammatory disorder of the airways associated with bronchial hyperresponsiveness, airway obstruction, and increased mucus production, with a predominance of type 2 immune response (Th2). According to the hygiene hypothesis, exposure to environmental bacterial lipopolysaccharide (LPS) may induce a type 1 immune response (Th1), modulating the development of asthma. Objective: In this study we investigated cytokine production by peripheral blood mononuclear cells (PBMC) from children and adolescents with severe asthma, in response to LPS stimulation in vitro. Materials and methods: 26 children were selected: 13 severe asthmatics and 13 healthy controls, aged between 5 and 18 years. They were evaluated through routine medical history, physical examination and lung function test to diagnose severe asthma. Allergy status was confirmed by skin prick test and specific IgE assay. We collected blood samples to analyse in vitro LPS-induced cytokines release by PBMC. Results: PBMC from severe asthmatic children produced lower levels of IL-12p70 in basal conditions and after 12 and 24 h stimulation with LPS compared to healthy controls. PBMC from severe asthmatic children produced lower levels of IL-4 after 24 h LPS stimulation compared to healthy controls. PBMC from severe asthmatic children produced more levels IL-17 and IL-10 after stimulus with LPS compared to healthy controls. The release of IFN-γ, IL-5 and TNF-α by PBMC from severe asthmatic children was similar to healthy controls. Conclusion: Our results demonstrate that LPS directly influence the cytokine profile of PBMC in children with severe asthma. These observations may be potentially helpful in developing new treatment strategies (AU)


No disponible


Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Asma/imunologia , Células Th2 , Células Th1 , Leucócitos Mononucleares , Interleucina-4 , Interleucina-12 , Interferon gama , Linfotoxina-alfa , Lipopolissacarídeos , Monitoramento Epidemiológico/tendências , Interleucina-5 , Interleucina-10 , Interleucina-17 , Citocinas , Hipersensibilidade , Brasil/epidemiologia
14.
Clin. transl. oncol. (Print) ; 17(8): 590-595, ago. 2015. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-138173

RESUMO

Objective. Vitamin D deficiency is reported to be involved in pathogenesis of ovarian cancer. But the mechanism is yet to be explored. An imbalance between Th1 and Th2 activity play a crucial role in pathogenesis of many cancers. The purpose of the study is to find out the Th1/Th2 status by estimating TNF-α (Th1 marker) and IL-4 (Th2 marker) in ovarian cancer cases and controls and to correlate these with serum vitamin D levels. Materials and methods. A case–control study with 50 ovarian cancer cases and 50 healthy controls was conducted. The cytokines TNF-α and IL-4 were estimated by ELISA. Serum vitamin D was measured by electro-chemiluminescence immunoassay method. Results. Median TNF-α levels (12.2 vs 6.2 pg/ml; p value <0.001) were significantly higher in ovarian cancer patients and mean IL-4 levels (2.22 ± 0.51 vs 2.99 ± 0.68 pg/ml; p value <0.05) were significantly lower as compared to those of controls. Levels of TNF-α and IL-4 did not vary significantly with clinical staging, and histological grading. Vitamin D levels were negatively correlated with TNF-α and positively correlated with IL-4. Conclusions. Low vitamin D levels promotes Th1 activity increasing TNF-α levels and inhibits Th2 activity decreasing IL-4 levels in ovarian cancer. These low levels of vitamin D may induce pro-inflammatory micro ambience which might contribute to pathogenesis of ovarian cancer (AU)


No disponible


Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/dietoterapia , Neoplasias Ovarianas/patologia , Vitamina D/uso terapêutico , Citocinas/metabolismo , Interleucina-4/uso terapêutico , Ovário , Ovário/patologia , Epitélio , Vitamina D/metabolismo , Imunoensaio/métodos , Estudos de Casos e Controles , Inquéritos e Questionários , Modelos Lineares , Análise de Regressão
15.
Allergol. immunopatol ; 43(4): 376-382, jul.-ago. 2015. tab, graf
Artigo em Inglês | IBECS | ID: ibc-139364

RESUMO

Background: Acute bronchiolitis comprises a major cause for morbidity in infants with viral infection which induces an immune inflammatory response that may produce long lasting harmful effects. Currently, there is no effective therapy for bronchiolitis. Objective: Our aim was to investigate the efficacy of five-day montelukast therapy in acute bronchiolitis management. Methods: The study included 50 infants with acute bronchiolitis. The infants with first episode of acute bronchiolitis were randomly assigned to receive daily montelukast dose of 4 mg over five days after admission or no treatment. Plasma eotaxin, IL-4, IL-8 and IFN-gamma levels were evaluated before and after treatment by ELISA method. In the present study, the primary outcome measure was change in clinical severity score, whilst secondary outcome measures were changes in plasma eotaxin, IL-4, IL-8, IFN-gamma levels. Results: No significant differences was found in clinical severity score with five-day montelukast treatment (p > 0.05, Mann–Whitney U test). There were no significant differences in plasma eotaxin, IL-4, IL-8, IFN-gamma levels between the groups (p > 0.05 Mann–Whitney U test). There was significant decrease in plasma IFN-gamma levels following five-day montelukast treatment (p = 0.027, Wilcoxon). There were no significant differences in plasma IL-4, IL-8, IFN-gamma levels between the groups after five-day montelukast treatment (p > 0.05, Wilcoxon). There was significant increase in eotaxin levels after five-day montelukast treatment (p = 0.009, Wilcoxon). Conclusion: Our study showed that montelukast affected plasma IFN-gamma and eotaxin levels after five days of treatment. Further studies are needed to demonstrate effects of montelukast on chemokine levels in bronchiolitis (AU)


No disponible


Assuntos
Humanos , Lactente , Bronquiolite/tratamento farmacológico , Citocinas , Albuterol/farmacocinética , Antagonistas de Leucotrienos/farmacocinética , Interleucina-8 , Interleucina-4/análise , Fatores de Necrose Tumoral/análise , Estudos Prospectivos
16.
Inmunología (1987) ; 33(2): 41-50, abr.-jun. 2014. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-125464

RESUMO

BACKGROUND: Changes in various cytokine activities have been reported during both HBV and HCV infections, while an imbalance of pro-inflammatory and anti-inflammatory cytokine production influences their immunopathogenesis. The aims of the present study are (a) to measure serum levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), interleukin-10 (IL-10), interleukin-2 (IL-2) and interleukin-4 (IL-4) in a sample of patients affected either by chronic HBV infection or by chronic HCV infection and in healthy controls (b) to correlate serum levels of IL-6, TNF-α, IL-10, IL-2 and IL-4 with biochemical markers of liver disease and (c) to evaluate differences of the aforementioned cytokines between HBV and HCV patients, as well as between patients and healthy controls. METHODS: The study population consisted of 50 patients with chronic hepatitis B, 40 patients with chronic hepatitis C and 30 healthy controls aged between 28 and 75 years. Biochemical markers of liver disease were evaluated by routine methods approved by IFCC. Serum concentrations of IL-6, TNF-α, IL-10, IL-2 and IL-4 were determined with the Human Cytokine/Chemokine Panel I Merck Millipore. RESULTS: HBV patients showed statistically significant difference in TNF-α and IL-2 levels, versus healthy controls. HCV patients showed statistically significant difference in TNF-α, IL-10 and IL-2 levels versus healthy controls. IL10 and IL-2 levels were significantly different between HBV and HCV patients. CONCLUSIONS: This study evaluated the serum cytokine levels (IL-6, TNF-α, IL-10, IL-2 and IL-4) of chronic hepatitis B or C patients, as well as the differences in such levels between patients and healthy controls. Correlations of cytokine levels with biochemical markers of liver disease were also observed, reflecting the degree of activity of the inflammatory process in the liver


ANTECEDENTES: Tanto en las infecciones por VHB como por VHC se han notificado cambios en las diversas actividades de las citocinas, y es conocido que su inmunopatogénesis está influida por un desequilibrio en la producción de citocinas pro y antiinflamatorias. Los objetivos del presente estudio son: a) medir las concentraciones séricas de interleucina 6 (IL-6), factor de necrosis tumoral α (TNF-α), interleucina 10 (IL-10), interleucina 2 (IL-2) e interleucina 4 (IL-4) en una muestra de pacientes afectados, ya sea por una infección crónica por VHB o por VHC y en controles sanos; b) correlacionar las concentraciones séricas de IL-6, TNF-α, IL-10, IL-2 e IL-4 con los marcadores bioquímicos de enfermedad hepática, y c) evaluar las diferencias de las citocinas antes mencionadas entre los pacientes con VHB y con HCV, así como entre los pacientes y los controles sanos. MÉTODOS: La población del estudio consistió en 50 pacientes con hepatitis B crónica, 40 pacientes con hepatitis C crónica y 30 controles sanos de edades comprendidas entre 28 y 75 años. Se evaluaron los marcadores bioquímicos de la enfermedad hepática mediante métodos rutinarios aprobados por la IFCC. Las concentraciones séricas de IL-6, TNF-α, IL-10, IL-2 e IL-4 se determinaron mediante el Panel I de citocinas/quimiocinas humanas de Merck Millipore. RESULTADOS: Los pacientes con VHB mostraron diferencias estadísticamente significativas en las concentraciones de TNF-α e IL-2, comparadas con las de controles sanos. Los pacientes con HCV mostraron diferencias estadísticamente significativas en TNF-α, IL-10 e IL-2 respecto a las concentraciones de los controles sanos. Las concentraciones de IL-10 e IL-2 fueron significativamente diferentes entre los pacientes con VHB y con HCV. CONCLUSIONES: Este estudio evaluó las concentraciones séricas de citocinas (IL-6, TNF-α, IL-10, IL-2 e IL-4) de pacientes con hepatitis crónica B o C, así como las diferencias en dichas concentraciones entre pacientes y controles sanos. También se observaron correlaciones de las concentraciones de citocinas con marcadores bioquímicos de la enfermedad hepática, lo que refleja el grado de actividad del proceso inflamatorio en el hígado


Assuntos
Humanos , Masculino , Feminino , Hepatite C Crônica/imunologia , Hepatite B Crônica/imunologia , Citocinas/análise , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangue , Interleucina-4/sangue , Interleucina-2/sangue , Interleucina-10/sangue , Estudos de Casos e Controles
17.
J. investig. allergol. clin. immunol ; 24(2): 114-121, mar.-abr. 2014. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-122271

RESUMO

Objective: The association between the interleukin 4 (IL-4) gene -33C/T polymorphism and asthma risk is a subject of debate. We conducted a meta-analysis to evaluate the association between this polymorphism and asthma susceptibility. Materials and Methods: A systematic search of electronic databases (Pubmed, EMBASE, Wanfang, China National Knowledge Infrastructure, and Weipu) was performed, and 18 studies involving 5523 cases and 5618 controls were identified. ORs with 95% CIs were used to assess the strength of association. Results: A significant association between the -33C/T polymorphism and asthma susceptibility was observed for TT vs CT + CC (OR, 1.16; 95% CI, 1.05-1.28; P=.005). In the subgroup analysis by race, a significant association was found among whites (OR, 1.71; 95% CI, 1.14- 2.57; P=.01) and Asians (OR, 1.14; 95% CI, 1.01-1.28; P=.04) but not among African Americans. In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR, 1.05; 95% CI, 0.89-1.24; P=.54) or nonatopic asthma patients (OR, 1.16; 95% CI, 0.81-1.67; P=.42). In the age-stratified analysis, an increased asthma risk was found in children (OR, 1.28; 95% CI, 1.01-1.63; P=.04) but not in adults. Conclusions: The results of this meta-analysis suggest that the IL-4 -33C/T polymorphism is a risk factor for asthma (AU)


Introducción: La asociación entre el polimorfismo -33C/T del gen de la interleucina-4 (IL-4) y el riesgo de presentar asma bronquial es un tema conflictivo. En este trabajo se realiza un meta-análisis con el fin de evaluar dicha asociación. Material y métodos: Se realizó una búsqueda sistemática en bases de datos electrónicas (Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure [CNKI] and Weipu Database) identificando 18 estudios que agrupan 5523 casos y 5618 controles. Se analizaron las Odds ratios (ORs) con un intervalo de confianza (CIs) del 95% para cuantificar la fuerza de la asociación. Resultados: En cuanto a los resultados obtenidos se observa una asociación significativa entre el polimorfismo -33C/T y la susceptibilidad de presentar asma para TT vs. CT + CC (OR = 1.16, 95% CI 1.05 - 1.28, P = 0.005). En el análisis de la etnicidad se observó una asociación significativa en caucásicos (OR = 1.71, 95% CI 1.14 - 2.57, P = 0.01) y asiáticos (OR = 1.14, 95% CI 1.01 - 1.28, P = 0.04) pero no en africanos americanos. En el análisis del estatus atópico no se encontró asociación significativa en pacientes con asma atópica (OR = 1.05, 95% CI 0.89 -1.24, P = 0.54) ni en pacientes con asma no atópica (OR = 1.16, 95% CI 0.81- 1.67, P = 0.42). En el análisis realizado según la edad se encontró un aumento de riesgo de padecer asma en los niños (OR = 1.28, 95% CI 1.01 - 1.63, P = 0.04) pero no en adultos. Conclusión: Este meta-análisis sugiere que el polimorfismo -33C/T del gen de la IL-4 constituye un factor de riesgo para padecer asma (AU)


Assuntos
Humanos , Asma/genética , Interleucina-4/genética , Fatores de Risco , Polimorfismo Genético , Marcadores Genéticos
18.
J. investig. allergol. clin. immunol ; 23(2): 107-111, mar.-abr. 2013. tab
Artigo em Inglês | IBECS | ID: ibc-111787

RESUMO

Introducción y objetivo: La IL-4 es una citocina que media las reacciones alérgicas. Diferentes polimorfismos en nucleótidos simples (SNPs) pueden influir sobre la respuesta mediada por citocinas. El motivo de este trabajo fue investigar la posible asociación de polimorfismos de la IL-4 con rinitis alérgica (RA) o asma atópica. Método: Se incluyó un total de 214 pacientes atópicos (asma n=108, RA n=106) y 120 controles sanos de Paquistán que fueron genotipados para SNPs IL-4 C-589T (rs2243250), T+2979G (rs2227284) y C-33T (rs2070874) mediante PCR. El análisis estadístico se llevó a cabo mediante el paquete StatCalc, EpiInfo v.6. Resultados: Observamos que el SNPs rs2243250 se asocia de forma significativa a asma (p 0.004; X2=11.0) y a RA (p<0.001; X2=20.2). Los genotipos más frecuentes en asma y RA fueron TT para SNP rs2243250, y GG para SNP rs2227284. Por otra parte, el SNP rs2070874 no se asocia con ninguna enfermedad respiratoria en una cohorte pakistaní. Conclusiones: rs2243250 y rs2227284 se asocian significativamente a asma y a RA. Los resultados de este estudio demuestran que además de los factores ambientales, los factores genéticos de riesgo juegan un papel importante en el desarrollo de las enfermedades atópicas respiratorias (AU)


Background and Objective: Interleukin (IL) 4 is a cytokine that mediates allergic responses. Different single nucleotide polymorphisms (SNPs) can influence the immune response mediated by cytokines. The aim of the present study was to investigate the possible association between IL-4 polymorphisms and allergic rhinitis and atopic asthma. Methods: A total of 214 atopic patients (108 with asthma and 106 with allergic rhinitis) and 120 healthy controls from Pakistan were genotyped for IL-4 SNPs C-589T (rs2243250), T+2979G (rs2227284), and C-33T (rs2070874) using restriction fragment length polymorphism-polymerase chain reaction. Statistical analysis was performed using the statistical software package StatCalc, EpiInfo v.6. Results: The SNP rs2243250 was significantly associated with both asthma (P=.004, X2=11.0) and allergic rhinitis (P<.001, X2=20.2), as was T-2979G (P<.001, 􀆵2=22.51 for asthma and P<.001, 􀆵2=57.6 for allergic rhinitis). The most frequent genotypes in the asthma and allergic rhinitis groups were TT for SNP rs2243250, and GG for SNP rs2227284. rs2070874 was not found to be associated with either of the 2 atopic respiratory diseases analyzed in the Pakistani cohort. Conclusions: rs2243250 and rs2227284 are significantly associated with asthma and allergic rhinitis. The results of this study indicate that in addition to environmental factors, genetic risk factors also play an important role in the development of atopic respiratory diseases (AU)


Assuntos
Humanos , Interleucina-4/genética , Polimorfismo Genético , Hipersensibilidade Imediata/genética , Asma/genética , Rinite Alérgica Perene/genética , Paquistão , Hipersensibilidade Respiratória/genética , Fatores de Risco
19.
Allergol. immunopatol ; 40(2): 81-87, mar.-abr. 2012.
Artigo em Inglês | IBECS | ID: ibc-97587

RESUMO

Background: Polymorphonuclear neutrophils (PMNs) were originally described as short lived and terminally differentiated phagocytes that contribute only to the innate immune response. Some studies of PMNs cytokine production and expression of numerous cell surface proteins has suggested that PMNs are likely to influence adaptive responses and may satisfy the criteria of antigen presenting cells.Aim of the study This work aimed to study the effect of IL-4 in the function of PMNs as antigen presenting cells. Methods: Flow cytometry was used in the present study for the detection of cell surface human leukocyte antigen (HLA) class II, CD80 and CD86 required for antigen presentation and subsequent T-cell activation in the presence of Staphylococcus aureus enterotoxin (A). Human peripheral blood neutrophils were used for this purpose. Results: This study has shown that IL-4 stimulated PMNs for 24h expressed HLA class II, CD80 and CD86 that involved in antigen presentation. It also indicated that co-cultivation of IL-4 stimulated PMNs with autologous T-cells and in the presence of S. aureus enterotoxin (A) induced T-cell proliferation. Conclusions: In vitro stimulation of PMNs with IL-4 showed expression of surface molecules involved in antigen presentation. In addition, the co-culture of T-Cells and stimulated PMNs showed high T-Cells proliferation in the presence of superantigens(AU)


Assuntos
Humanos , Linfócitos T , Proliferação de Células , Antígenos HLA/análise , Superantígenos/análise , Imunidade Inata/imunologia , Proteínas de Membrana , Interleucina-4/farmacocinética , Staphylococcus aureus/patogenicidade
20.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 38(6): 229-233, nov.-dic. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-115788

RESUMO

Objetivo: Comparar las concentraciones de interleucina 4 en pacientes con preeclampsia y embarazadas normotensas sanas. Material y método Se seleccionó un total de 100 pacientes. Se incluyeron a 50 pacientes preeclámpticas como los casos (grupo A) y un grupo control que fue seleccionado por tener una edad y un índice de masa corporal similares al grupo de estudio, y consistió en 50 embarazadas sanas (grupo B). Las muestras de sangre para la determinación de interleucina 4 se recolectaron en todas las pacientes antes del parto e inmediatamente después del diagnóstico en el grupo de casos. Resultados No se encontraron diferencias significativas en relación con la edad materna, edad gestacional e índice de masa corporal al momento de la toma de la muestra (p=ns). Se observaron diferencias estadísticamente significativas entre los grupos en los valores promedio de presión (..) (AU)


Objective: To compare concentrations of interleukin-4 in patients with preeclampsia and healthy normotensive pregnant women. Material and methods: One hundred patients were selected. Fifty preeclamptic patients were selected as cases (group A) and 50 healthy pregnant women with a similar age and bodymass index to those in the study group were selected as controls (group B). Blood samples for interleukin-4 determination were collected in all patients before labor and immediately after diagnosis in the study group. Results: There were no significant differences in maternal or gestational age or body mass index at sample collection (p=ns). Significant differences were found between (..) (AU)


Assuntos
Humanos , Feminino , Gravidez , Interleucina-4/análise , Pré-Eclâmpsia/fisiopatologia , Estudos de Casos e Controles , Citocinas/análise , Inflamação/fisiopatologia
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